Featured Research

from universities, journals, and other organizations

'Normalizing' Tumor Vessels Leaves Cancer More Benign

Date:

February 21, 2009

Source:

Cell Press

Summary:

New research suggests a counterintuitive new method to make cancer less likely to spread: by normalizing the shape of tumors' blood vessels to improve their oxygen supply. Such a treatment strategy might also boost the efficacy and reduce resistance to available anti-cancer drugs and so-called anti-angiogenic drugs that work by cutting off the growth of new blood vessels.

Share This

A new report suggests a counterintuitive new method to make cancer less likely to spread: by normalizing the shape of tumors' blood vessels to improve their oxygen supply. Such a treatment strategy might also boost the efficacy and reduce resistance to available anti-cancer drugs and so-called anti-angiogenic drugs that work by cutting off the growth of new blood vessels.

Related Articles

"In tumors, the endothelial cells lining blood vessels grow in all directions and over each other," said Peter Carmeliet of Vesalius Research Center. Irregular shape and gaps left in the vessel walls also make them leaky.

Tissues need oxygen delivered by the bloodstream to grow. But, in the case of tumors, that haphazard overgrowth of blood vessels and deteriorated endothelial lining impairs their own ability to function, he continued. As a result, tumors become more and more oxygen deprived – a condition that is a "driving force" for cancer cells to escape and spread to other parts of the body.

That vicious cycle might be halted with treatments designed to target an oxygen-sensing enzyme known as PHD2 in the linings of tumors' blood vessels, Carmeliet's team now finds. The new results also offer fundamental new insight into blood vessel biology.

Indeed, numerous earlier studies had examined how blood vessels arise, branch and elongate at the molecular level. However, little was known about how vessels regulate their shape.

Since supply of oxygen is one of the most basic functions of vessels, the researchers also suspected that they should possess ways to sense and re-adapt oxygen supply in the case of a shortage. They looked to a newly discovered class of oxygen sensors: the prolyl hydroxylase domain proteins, PHD1-3.

In the current study, Carmeliet's group focused on the role of PHD2 in balancing oxygen levels by influencing the characteristics of blood vessels. In mice with half the normal amount of PHD2 in the endothelial cells that line blood vessels, tumor vessels were found in the same numbers and sizes. However, the shape and structure of those vessels was more "normal," with linings made up of tightly aligned, orderly shaped and smooth cells having a cobblestone appearance.

That more regular vessel structure improved tumors' oxygen supply, leading to physiological changes that counteracted the overall malignancy of the cancer, they report. The cells were better able to counterbalance the "abnormalizing" effects of the tumors, and halt the progression to metastasis.

The findings in mice may have medical implications. "By normalizing the tumor vasculature, partial loss of PHD2 may shift tumors from an aggressive metastasizing tumor type to a more benign, well-encapsulated tumor," the researchers said. The partial loss of PHD2 doesn't seem to affect the blood vessels of healthy tissues, they said, suggesting a PHD2 inhibitor might selectively target tumor vessels.

Working to keep a tumor well-supplied with a key nutrient like oxygen may seem counterintuitive, but such a therapy might also be an advantageous addition to existing treatment regimens, Carmeliet added, noting that chemotherapeutic drugs and radiation depend on adequate oxygen levels to work. Targeting PHD2 might also help to avoid a potential pitfall of anti-angiogenic drugs that attempt to "starve" tumors by pruning back their blood vessel supply. "You have to be careful," he said. "If you prune too many vessels, leaving tumors overly hypoxic, it may induce their resistance."

This research might also open new methods of treatment for disorders that are accompanied by a shortage of oxygen, such as myocardial infarction or stroke. The researchers also hope to be able to use this discovery to tackle the morbid growth of blood vessels in the retina.

This research was purblished online on February 12th in the journal Cell.

Story Source:

The above story is based on materials provided by Cell Press. Note: Materials may be edited for content and length.

More From ScienceDaily

More Health & Medicine News

Featured Research

Mar. 3, 2015  New assays can detect malaria parasites in human blood at very low levels and might be helpful in the campaign to eradicate malaria, reports a new study. An international team led by Ingrid Felger, ... full story

Mar. 3, 2015  Adults over the age of 30 only catch flu about twice a decade, a new study suggests. So, while it may feel like more, flu-like illness can be caused by many pathogens, making it difficult to assess ... full story

Mar. 3, 2015  No significant change in home habits of smokers have been observed in the aftermath of a ban on smoking in public spaces, researchers report. Greater inspiration to kick the habit likely comes from ... full story

Mar. 3, 2015  Heart function has been associated with the development of dementia and Alzheimer's disease through a new study. Participants with decreased heart function, measured by cardiac index, were two to ... full story

Mar. 3, 2015  Children of recently separated or divorced families are likelier to drink sugar-sweetened beverages than children in families where the parents are married, putting them at higher risk for obesity ... full story

Mar. 3, 2015  Gastric bypass and similar stomach-shrinking surgeries are a popular option for obese patients looking to lose weight or treat type 2 diabetes. While the surgeries have been linked to a decreased ... full story

Mar. 3, 2015  Most people consume more salt than they need and therefore have a higher risk of heart disease and stroke, which are the two leading causes of death worldwide. But a new study reveals that dietary ... full story

Mar. 3, 2015  Twice as many children born to mothers who took antibiotics during pregnancy were diagnosed with asthma by age 3 than children born to mothers who didn’t take prenatal antibiotics, a new study has ... full story

Mar. 3, 2015  Although sedatives are often administered before surgery, a randomized trial finds that among patients undergoing elective surgery under general anesthesia, receiving the sedative lorazepam before ... full story

Featured Videos

Mom Triumphs Over Tragedy, Helps Other Families

AP (Mar. 3, 2015)  After her son, Dax, died from a rare form of leukemia, Julie Locke decided to give back to the doctors at St. Jude Children&apos;s Research Hospital who tried to save his life. She raised $1.6M to help other patients and their families. (March 3)
Video provided by AP

Looted and Leaking, South Sudan's Oil Wells Pose Health Risk

AFP (Mar. 3, 2015)  Thick black puddles and a looted, leaking ruin are all that remain of the Thar Jath oil treatment facility, once a crucial part of South Sudan&apos;s mainstay industry. Duration: 01:13
Video provided by AFP

Woman Convicted of Poisoning Son

AP (Mar. 3, 2015)  A woman who blogged for years about her son&apos;s constant health woes was convicted Monday of poisoning him to death by force-feeding heavy concentrations of sodium through his stomach tube. (March 3)
Video provided by AP

Related Stories

Aug. 11, 2014  The anti-cancer effect of the antimalarial agent chloroquine when combined with conventional chemotherapy has been well documented. To date, it was assumed that chloroquine increases the sensitivity ... full story

Aug. 14, 2012  Researchers have confirmed their hypothesis that normalizing blood vessels by blocking oxygen sensor PHD2 would make chemotherapy more effective. They also demonstrated for the first time that this ... full story

Aug. 13, 2012  Since anti-cancer drugs are carried to tumors by the bloodstream, abnormal blood vessel development can hamper delivery. Medical researchers have found a molecule that promotes tumor vessel ... full story

June 6, 2011  Scientists in Australia have discovered a key molecule needed to kill the blood vessels that supply tumors. The research team found that for anti-cancer therapies that target tumor blood vessels to ... full story

ScienceDaily features breaking news and videos about the latest discoveries in health, technology, the environment, and more -- from major news services and leading universities, scientific journals, and research organizations.